This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Experimental studies reveal that certain populations (women, astronauts, patients) demonstrate lower orthostatic tolerance;however, the mechanism(s) remain unclear. Limited data suggests the redistribution of blood volume during an orthostatic challenge may play a role. During head-up tilt, ~700 ml of blood translocates to the lower abdomen, legs, buttocks, and pelvis. The abdominal/pelvic region includes the splanchnic bed, a highly compliant region. Blood pooling in this region is sequestered from the general circulation, challenging blood pressure maintenance. We have developed a quantitative approach that relates changes in blood volume distribution to cardiac filling. The circulation contains a volume indifferent point (VIP), a point where blood volume remains unchanged, regardless of posture. The vertical distance between the right atrium and the VIP determines the filling pressure or volume available to the heart. We have previously located the VIP and have shown that it can be moved closer to heart, which relates to improvements in orthostatic tolerance. The purpose of this study is to experimentally shift the location of VIP inferiorly similar to what might occur in populations susceptible to orthostatic intolerance. We will also determine the relationship between the location of the VIP and orthostatic tolerance.